myeloid derived suppressor cells and chronic myeloid leukemia

Conditions: Chronic Myeloid Leukemia Patients

Summary: the suppression of the immune system creates a permissive environment for development and progression of cancer. one population of immunosuppressive cells that have become the focus of intense study is myeloid derived suppressor cells , immature myeloid cells able to induce immune-escape, angiogenesis, and tumor progression. two different subpopulations have been identified and studied: granulocytic and monocytic myeloid derived suppressor cells with a different immunophenotype and immunosuppressive properties

myeloid-derived suppressor cells utilize different mechanisms to block both innate and adaptive arms of anti-tumour immunity, mostly through inhibition of t cell activation and expansion . human monocytic myeloid derived suppressor cells are mostly identified as cd14+ cells with negative or low expression of hladr. and also express high levels of cd11b and cd33 antigen . human granulocytic myeloid derived suppressor cells are usually defined as cd66b+ cd11b+ cd15+ hladr- cells and display an intermediate expression of cd33 and a variable expression of cd11b, depending on their maturation stage . chronic myeloid leukemia (cml) is a hematological cancer, characterized by a reciprocal chromosomal translocation between chromosomes 9 and 22 \[t(9;22)\], producing the bcr-abl oncogene. tyrosine kinase inhibitors represent the standard of care for cml patients and exert a dual mode of action: direct oncokinase inhibition and restoration of effector-mediated immune surveillance, which is rendered dysfunctional in cml patients at diagnosis, prior to tki therapy. tkis such as imatinib, and more potent second-generation nilotinib and dasatinib induce a high rate of deep molecular response (dmr, bcr-abl1 ≤ 0.01%) in cml patients. as a result, the more recent goal of therapy in cml treatment is to induce a durable deep molecular response as a prelude to successful treatment-free remission . accumulation of both gr-mdscs and mo-mdscs cells has been found in the peripheral blood of chronic myeloid leukemia (cml) patients. they are part of the tumor clone showing bcr/abl expression. bcr-abl tyrosine kinase inhibitors (tki) are able to induce remission in cml patients but not to eliminate leukemia stem cells , which can regenerate leukemia on drug discontinuation . unfortunately, molecular relapse is observed after cessation of tyrosine kinase inhibitors in 61-66% of cml patients, previously in complete molecular response (presumably due to the reactivation of dormant cml lscs that are resistant to tki-induced leukemic cell ablation. thus, current research efforts aim to develop additional therapies to target these tki-refractory cml lscs . with the aim of increasing cure rates and make it possible for patients to discontinue treatment, tki therapies are currently evaluated in combination with immune modulators .

Eligibility criteria:
inclusion criteria: * all newly diagnosed chronic phase cml patients during one year in assiut university hospital. exclusion criteria: * preivously diagnosed cml patients . * other myeloproliferative disorders .